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| | ==Molecular mechanism of guidance cue recognition== | | ==Molecular mechanism of guidance cue recognition== |
| - | <StructureSection load='3nvq' size='340' side='right' caption='[[3nvq]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='3nvq' size='340' side='right'caption='[[3nvq]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3nvq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NVQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NVQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3nvq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NVQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nvn|3nvn]], [[3nvx|3nvx]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SEMA7A, CD108, SEMAL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PLXNC1, VESPR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nvq OCA], [https://pdbe.org/3nvq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nvq RCSB], [https://www.ebi.ac.uk/pdbsum/3nvq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nvq ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nvq OCA], [http://pdbe.org/3nvq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nvq RCSB], [http://www.ebi.ac.uk/pdbsum/3nvq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nvq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SEM7A_HUMAN SEM7A_HUMAN]] Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses. Promotes formation of focal adhesion complexes, activation of the protein kinase PTK2/FAK1 and subsequent phosphorylation of MAPK1 and MAPK3. Promotes production of proinflammatory cytokines by monocytes and macrophages. Plays an important role in modulating inflammation and T-cell-mediated immune responses. Promotes axon growth in the embryonic olfactory bulb. Promotes attachment, spreading and dendrite outgrowth in melanocytes.<ref>PMID:12879062</ref> <ref>PMID:17377534</ref> <ref>PMID:17671519</ref> [[http://www.uniprot.org/uniprot/PLXC1_HUMAN PLXC1_HUMAN]] Receptor for SEMA7A, for smallpox semaphorin A39R, vaccinia virus semaphorin A39R and for herpesvirus Sema protein. Binding of semaphorins triggers cellular responses leading to the rearrangement of the cytoskeleton and to secretion of IL6 and IL8 (By similarity).<ref>PMID:20727575</ref> | + | [https://www.uniprot.org/uniprot/SEM7A_HUMAN SEM7A_HUMAN] Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses. Promotes formation of focal adhesion complexes, activation of the protein kinase PTK2/FAK1 and subsequent phosphorylation of MAPK1 and MAPK3. Promotes production of proinflammatory cytokines by monocytes and macrophages. Plays an important role in modulating inflammation and T-cell-mediated immune responses. Promotes axon growth in the embryonic olfactory bulb. Promotes attachment, spreading and dendrite outgrowth in melanocytes.<ref>PMID:12879062</ref> <ref>PMID:17377534</ref> <ref>PMID:17671519</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nv/3nvq_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nv/3nvq_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[Plexin|Plexin]] | + | *[[Plexin 3D structures|Plexin 3D structures]] |
| - | *[[Semaphorin|Semaphorin]] | + | *[[Semaphorin 3D structures|Semaphorin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chen, X]] | + | [[Category: Large Structures]] |
| - | [[Category: Focia, P]] | + | [[Category: Chen X]] |
| - | [[Category: Garcia, C]] | + | [[Category: Focia P]] |
| - | [[Category: He, X]] | + | [[Category: Garcia C]] |
| - | [[Category: Juo, Z]] | + | [[Category: He X]] |
| - | [[Category: Liu, H]] | + | [[Category: Juo Z]] |
| - | [[Category: Shim, A]] | + | [[Category: Liu H]] |
| - | [[Category: Beta-propeller]]
| + | [[Category: Shim A]] |
| - | [[Category: Signaling]]
| + | |
| - | [[Category: Signaling protein-protein binding complex]]
| + | |
| Structural highlights
Function
SEM7A_HUMAN Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses. Promotes formation of focal adhesion complexes, activation of the protein kinase PTK2/FAK1 and subsequent phosphorylation of MAPK1 and MAPK3. Promotes production of proinflammatory cytokines by monocytes and macrophages. Plays an important role in modulating inflammation and T-cell-mediated immune responses. Promotes axon growth in the embryonic olfactory bulb. Promotes attachment, spreading and dendrite outgrowth in melanocytes.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Repulsive signaling by Semaphorins and Plexins is crucial for the development and homeostasis of the nervous, immune, and cardiovascular systems. Sema7A acts as both an immune and a neural Semaphorin through PlexinC1, and A39R is a Sema7A mimic secreted by smallpox virus. We report the structures of Sema7A and A39R complexed with the Semaphorin-binding module of PlexinC1. Both structures show two PlexinC1 molecules symmetrically bridged by Semaphorin dimers, in which the Semaphorin and PlexinC1 beta propellers interact in an edge-on, orthogonal orientation. Both binding interfaces are dominated by the insertion of the Semaphorin's 4c-4d loop into a deep groove in blade 3 of the PlexinC1 propeller. A39R appears to achieve Sema7A mimicry by preserving key Plexin-binding determinants seen in the mammalian Sema7A complex that have evolved to achieve higher affinity binding to the host-derived PlexinC1. The complex structures support a conserved Semaphorin-Plexin recognition mode and suggest that Plexins are activated by dimerization.
Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1.,Liu H, Juo ZS, Shim AH, Focia PJ, Chen X, Garcia KC, He X Cell. 2010 Sep 3;142(5):749-61. Epub 2010 Aug 19. PMID:20727575[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pasterkamp RJ, Peschon JJ, Spriggs MK, Kolodkin AL. Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature. 2003 Jul 24;424(6947):398-405. PMID:12879062 doi:http://dx.doi.org/10.1038/nature01790
- ↑ Suzuki K, Okuno T, Yamamoto M, Pasterkamp RJ, Takegahara N, Takamatsu H, Kitao T, Takagi J, Rennert PD, Kolodkin AL, Kumanogoh A, Kikutani H. Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin. Nature. 2007 Apr 5;446(7136):680-4. Epub 2007 Mar 21. PMID:17377534 doi:http://dx.doi.org/10.1038/nature05652
- ↑ Scott GA, McClelland LA, Fricke AF. Semaphorin 7a promotes spreading and dendricity in human melanocytes through beta1-integrins. J Invest Dermatol. 2008 Jan;128(1):151-61. Epub 2007 Aug 2. PMID:17671519 doi:http://dx.doi.org/10.1038/sj.jid.5700974
- ↑ Liu H, Juo ZS, Shim AH, Focia PJ, Chen X, Garcia KC, He X. Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1. Cell. 2010 Sep 3;142(5):749-61. Epub 2010 Aug 19. PMID:20727575 doi:10.1016/j.cell.2010.07.040
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